Research and development in the field of contraception in humans has been in the areas of physical and chemical barriers to sperm transport, such as vaginal foams, diaphragms, intrauterine devices, and condoms, and in the area of oral contraceptives containing one or more steroid hormones. Oral contraceptives have been developed which are highly effective in preventing contraception, and today more than fifty million women around the world use oral contraceptives. Typically, the oral contraceptives take the form of a combination of an estrogen and a progestogen (also known as progestin). In some of these regimens, known as combination regimens, a consistent dose of an estrogen and a progestogen is administered daily throughout the period of administration. In other regimens, referred to as sequential regimens, the amount of estrogen or progestogen or both is increased or decreased during the menstrual cycle. Some sequential regimens provide two-stage or bi-phasic control. (See, for example, U.S. Pat. No. 3,969,502). Others provide a three-stage or tri-phasic combination of components. (See, for example, U.S. Pat. Nos. 4,628,051; 4,390,531.) A third type of regimen also is known in which one or more progestogens is administered daily throughout the menstrual cycle.
The hormones in oral contraceptives act both within the central nervous system and in tissues of the urogenital tract to inhibit reproductive function. The principal sites of action are the hypothalamus and pituitary to prevent the midcycle surge of luteinizing hormone (LH) and hence to prevent ovulation. The basal concentrations of LH and follicle-stimulating hormone (FSH) and plasma levels of estradiol and progestrone are suppresed in users of oral contraceptives. In essence, these contraceptives work by causing changes in hormone levels that imitate those caused by pregnancy. This effect is dose dependent. These conventional oral contraceptives are administered for a minimum of 21 days of a woman's cycle, and in some instances for the entire 28-30 days of the cycle.
Oral contraceptives also exert a direct effect on the urogenital tract. They alter the structure and physical-chemical composition of the endometrium and the consistency of the cervical mucous, thus altering the uterine capacity for the ovum to implant.
Oral contaceptives have been shown to provide benefits other than the prevention of pregnancy. Compared to non-users, women who take oral contraceptives have been shown to have a lower risk of pelvic inflammatory disease (PID), ectopic pregnancy, endometrial cancer, and benign breast disease. Most significantly, the current combination-type contraceptives also are responsible for reducing the incidence of ovarian cancer. Oral contraceptives also can provide relief from common menstrual disorders, including irregular menses, premenstrual tension, excess blood loss and cramps.
Use of conventional oral contraceptives, however, also is attended by certain risks. These risks, which include a greater chance of suffering from venous thromboembolism, ischemic heart disease, cerebrovascular disease and hypertension, are believed to be largely due to the estrogen component (typically ethinyl estradiol or menstranol) in the contraceptives. The risk of suffering from any of these conditions has been found to be confined primarily to women over age 35, especially to women over age 35 who smoke. Women who take estrogen also may suffer other negative side effects, including gastrointestinal disturbances, nausea and weight gain.
In an effort to avoid the negative side effects or possible side effects associated with oral contraceptives containing estrogen, oral contraceptives containing only one or more progestogens as the active component have been developed. These contraceptives, however, generally have been found to be less effective than those containing both an estrogen and a progestogen. One common side effect suffered by women who take oral contraceptives which contain only progestogen is breakthrough bleeding during the menstrual cycle.
In view of the drawbacks and negative side effects of conventional oral contraceptives, new contraceptives are sought. Accordingly, it is an object of the present invention to provide a contraceptive method which is highly effective and provides the benefits and avoids the adverse effects associated with contraceptives currently used. It also is an object of this invention to provide a method of reducing the incidence of breast cancer in women.